tbuckley/cabot-search huggingface dataset:
Abstract 12252: Trends of Arrhythmias in Delivery Hospitalizations in the United States
Authors: Aarti Thakkar, Yaa A Kwapong, Harsh P Patel, Roger S Blumenthal, Jonathan Chrispin, Katherine C Wu, Sourbha Dani, Garima Sharma
Journal: Circulation (2022)

Background: Cardiac arrhythmias are associated with increased maternal morbidity. Few data exist on trends of delivery-related hospitalizations complicated by arrhythmias. Methods: We used the National Inpatient Sample database to identify delivery hospitalizations for women ages 18-49 years between 2009 to 2019 and coding data from the 9 th and 10 th editions of the International Classification of Diseases to identify supraventricular tachycardias (SVT), atrial fibrillation (AF), atrial flutter, ventricular tachycardia (VT), and ventricular fibrillation (VF). Data were stratified by age, race/ethnicity, maternal comorbidities, hospital size and setting, and type of insurance coverage. Primary outcome was in-hospital mortality, secondary outcome was adverse pregnancy outcomes (APOs), cesarean section, and cardiovascular decompensation. Multivariate logistic regression was used to understand the predictors of arrhythmia during delivery hospitalization. Results: Among 41,320,000 delivery hospitalizations, 141,372 were complicated by arrhythmias; SVT (13%), AF (8%), and VT (3%). The incidence of arrhythmia increased between 2009-2014 and again from 2014-2019 ( Fig 1 ). Women above 30 years of age, with valvular disease, heart failure, obesity, hypertension, hyperlipidemia, diabetes mellitus, or previous MI had a greater likelihood of arrhythmia during delivery ( Fig 1 , all p &lt;0.0001). Though in-hospital mortality was low, maternal morbidity from cardiogenic shock (0.20 v 0.0%), caesarean section (44.6 v 32%), and APOs such as preeclampsia (9.36 v 3.57%) were increased (p &lt;0.0001) for women with arrhythmia. Conclusions: Women with known CV risk factors are more likely to experience arrhythmia during delivery. Those with arrhythmias also have an increased likelihood of cesarean sections, APOs and cardiogenic shock. The data highlight the importance of CVD risk factor modification and better pregnancy care for those at higher risk of morbidity.
Abstract 12158: Left Atrial Volumes and Strain by Cardiac Magnetic Resonance Are Associated With Long Term Outcomes in Patients With Hypertrophic Cardiomyopathy
Authors: Maria Khalil, Mina M Benjamin, Muhammad S Munir, Menhel Kinno, Mushabbar Syed
Journal: Circulation (2022)

Introduction: We sought to evaluate left atrial (LA) morphology, function and strain by cardiac magnetic resonance (CMR) in hypertrophic cardiomyopathy (HCM) patients and the association of these parameters with long-term clinical outcomes. Methods: We retrospectively evaluated 50 HCM patients and 50 patients without significant cardiovascular disease (controls) who underwent clinically-indicated CMR. We performed a multivariate regression analysis adjusting the model for age, coronary artery disease, NYHA class, late gadolinium enhancement and LV EF with endpoints of ventricular tachyarrhythmias (VTA) and heart failure hospitalization (HFH). LA indexed volumes (LAVi), LA EF, expansion index, reservoir (εR), conduit (εCD), and contractile strain (εCT) were measured. Results: The mean age for HCM patients was 59.6 ± 16.3 (54% males) versus 50.9 ± 14.6 (36% male) for controls. Median follow up was 15.6 months. HCM patients had significantly higher LV mass, LV wall thickness, LAVi and lower LA strain compared to controls. On multivariate analysis, LA εCT, minimum and maximum LAVi were significantly associated with the composite outcome (p = 0.05). Cox proportional hazard models (figure) showed a clear difference in the outcomes around median εCT and maximum LAVi. Conclusion: HCM patients had significantly higher LAVi and lower LA strain compared to controls. LA εCT, minimum and maximum LAVi were significantly associated with the composite outcome of VTA or HFH.
Abstract 12069: Spectrum and Prevalence of Attention Deficit Hyperactivity Disorder (ADHD) and Intentional ADHD-Directed Pharmacotherapy in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Sahej Bains, Johan M Bos, John Giudicessi, Ciorsti J MacIntyre, Michael J Ackerman
Journal: Circulation (2022)

Background: The estimated prevalence of attention-deficit/hyperactivity disorder (ADHD) globally is about 5%. For patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), ADHD-directed stimulant therapy is relatively contraindicated. However, previous studies have shown that use of these treatments is safe for patients with long QT syndrome, a similar genetic heart disease. Whether this is the same for patients with CPVT remains unknown. Objective: To evaluate ADHD-directed treatment, outcome, and frequency of CPVT-triggered events in patients with CPVT and concomitant ADHD. Methods: A retrospective electronic medical record review of 216 patients with CPVT evaluated in Mayo Clinic’s Windland Smith Rice Genetic Heart Rhythm Clinic was performed to determine the prevalence of concomitant ADHD and the incidence of CPVT-triggered events in these patients. Results: Overall, 14 patients (6%) were diagnosed with CPVT and concomitant ADHD (6 female, average age 19 ± 3 years). At the time of first evaluation, ADHD-directed stimulant therapy was stopped or advised against in 8/14 patients (57%). It was (re)started in 11 patients (79%) following comprehensive evaluation and treatment initiation for CPVT with pharmacologic therapy in 14/14 patients (100%), denervation surgery in 12 (86%), and an implantable cardioverter defibrillator in 4 (29%). Prior to Mayo Clinic evaluation, 10 patients (71%) treated for CPVT had a breakthrough cardiac event, without being on stimulant therapy, while 4 patients (29%) had an event while being treated for both CPVT and ADHD for an average time on stimulant therapy of 6 ± 6 years. Following CPVT treatment optimization and ADHD stimulant (re)initiation, patients have remained event-free for a total of 82 patient years (mean follow-up 6 ± 5 years). Conclusion: Among patients with CPVT, the prevalence of ADHD was similar to that in the general population, which can be treated safely and effectively with stimulant therapy. Although the rate of adverse events was low in stimulant-treated patients, physicians should weigh the potential effects of suboptimal treatment of ADHD with the theoretical proarrhythmic risk from stimulant medications on a case-by-case basis.
Abstract 12504: Outcomes of COVID-19 Positive Donor Heart Transplantation in the United States
Authors: Samuel T Kim, Mark R Helmers, Amit Iyengar, D. Alan Herbst, Noah Weingarten, Pavan Atluri
Journal: Circulation (2022)

Introduction: Small institutional case series have documented successful heart transplant outcomes using COVID-19 positive (COVID-19+) donor allografts. However, little is known regarding the impact of donor COVID-19 status on a national scale. In this study, we characterize outcomes of the first 84 COVID-19+ donor heart transplants in the United States. Methods: Retrospective analysis of the United Network for Organ Sharing database was performed for adult heart transplants from February 2021 to March 2022. Donor COVID-19+ status was defined as a positive nucleic acid amplification, antigen or other COVID-19 test within 7 days of transplant. Fisher’s exact test and Kaplan-Meier survival estimates were used to determine differences in outcomes, including graft failure, post-operative stroke and dialysis, length of stay and 30-day survival. Results: Overall, 3,289 heart transplants were included in analysis, with 84 utilizing COVID-19+ donor hearts. COVID-19+ allografts had similar cold ischemic times (3.7 vs 3.5 hours, P=0.22) compared to others. Recipients of COVID-19+ donor organs had similar lengths of stay (15 vs 17 days, P=0.19), rates of graft failure (2.4% vs 1.0%, P=0.22), post-operative stroke (0.0% vs 3.0%, P=0.18), post-operative dialysis (15.5% vs 13.4%, P=0.52) and 30-day post-transplant survival (96.1% vs 97.0%, P=0.63) compared to recipients of non-positive donors. Among the 4 deceased recipients of COVID-19+ allografts, none have died from pulmonary or infectious causes of death. Use of COVID-19+ donors for heart transplantation increased throughout the study period (r=0.79, Figure). Conclusions: Short-term outcomes of heart transplant recipients receiving COVID-19+ donor organs are reassuring, providing preliminary evidence that heart transplantation may be safely performed using appropriately selected COVID-19+ donor allografts. Continued monitoring for long-term outcomes and potential complications are warranted.
Abstract 11270: SGLT2 Expression in the Coronary Microvessel Endothelium and Cardiomyocytes of Cardiac Patients: Determinant Role of Low-Grade Inflammation and Induction of Endothelial Dysfunction
Authors: Ali MROUEH, Walaa Fakih, Dal-Seong GONG, Cyril Auger, Kensuke Matsushita, Olivier Morel, Jean-Philippe Mazzucotelli, Valerie Schini-Kerth
Journal: Circulation (2022)

Introduction: Sodium-glucose co-transporter2 inhibitors (SGLT2i) showed benefit in major cardiovascular diseases characterized by low-grade inflammation. However, the role and function of SGLT2 in the heart remain unclear. Hypothesis: This study evaluated whether SGLT1/2 are expressed in the heart of patients with cardiac diseases, and determined the role of low-grade inflammation and the functional consequences. Methods: Human left ventricle (LV) biopsies were collected from 17 patients with aortic and mitral valves stenosis or hypertrophic cardiomyopathy at Strasbourg Hospital. Cultured endothelial cells (EC) were from pig coronary arteries. Expression levels were assessed by RT-qPCR, Western blot analysis and immunofluorescence staining, and the level of oxidative stress and nitric oxide (NO) using fluorescent probes. Results: SGLT1/2 protein levels were observed in the LV of cardiac patients and correlated p-p65 NFκB levels. SGLT2, VCAM-1 and TNF-α staining was observed in the endothelium of coronary microvessels and, to some extent, cardiomyocytes. TNF-α upregulated SGLT1 and 2, VCAM-1, AT1R and ACE expression and decreased that of eNOS and the bradykinin-stimulated NO formation in EC. The stimulatory effect of TNF-α was inhibited by an NF-kB inhibitor and SGLT2 siRNA but not by SGLT1 siRNA. Oxidative stress in LV sections and TNF-α-treated EC was inhibited by VAS-2870 (NADPH oxidase inhibitor), losartan (AT1R antagonist) and empagliflozin (SGLT2i), and in LV by infliximab (TNF-α receptor inhibitor). Conclusions: The findings indicate that SGLT2 is expressed in the LV of cardiac patients in the coronary endothelium and cardiomyocytes, and associated with their low-grade inflammatory status. Moreover, TNF-α upregulated the AT1R/NAPDH oxidase/SGLT2 crosstalk to sustain oxidative stress promoting endothelial dysfunction. Thus, SGLT2 appears as an interesting target to protect the coronary microcirculation.
Abstract 11189: An Integrated Framework With Machine Learning and Radiomics Score for the Prediction of Coronary Artery Calcium Score From Chest Radiographs
Authors: Hyung-Bok Park, Hyunseok Jeong, Youngtaek Hong, Hyuk-Jae Chang
Journal: Circulation (2022)

Introduction: Recently introduced radiomics technology enables the detection of hidden information from commonly disregarded medical images, including CXR. Hypothesis: The purpose of this study was to evaluate the feasibility of a novel technique involving radiomics features combined with machine learning to identify moderate-to-severe coronary artery calcium (CAC) using simple chest X-ray radiography (CXR). Methods: We included 559 patients (women, 44.9%; mean age, 62.4 ± 9.4 years) from two independent clinical studies who underwent a calcium scan and CXR within 6 months. The total cohort was allocated to the training and validation cohorts in a 7:3 ratio, with all clinical characteristics well-matched, including the CAC score. Radiomics features were extracted from manually delineated cardiac contours, and a radiomics score formulation for the prediction of a CAC score ≥100 was generated using the machine learning method in the training cohort. To evaluate the incremental performance of the radiomics score, a basic clinical model including age, sex, and body mass index (model 1) and a radiomics score added model (model 2) were utilized. Results: The radiomics score was the most prominent predictive factor for CAC score ≥100 (odds ratio [OR] = 2.33; 95% confidence interval [CI] = 1.62-3.44; p &lt; 0.001). In the training cohort, model 2 demonstrated significant incremental validity in predicting CAC scores ≥100 compared to model 1 (area under the curve [AUC]; 0.73 vs. 0.69, p = 0.022). The performance of model 2 was also similar in both the training and validation cohorts (AUC 0.73, 95% confidence interval [CI] 0.68 - 0.78 vs. AUC 0.72, 95% CI 0.64 - 0.80). Conclusions: We developed a machine learning-based radiomics scoring model that could be utilized as a potential imaging marker for predicting CAC scores from CXR. This novel method may be widely applicable to clinical practice and can improve the pre-test probability of coronary artery disease.
Abstract 11587: Intriguing Genetic Overlap Between SCAD and TAD
Authors: Syeda Manahil Haider Jeoffrey Jeoffrey, Asanish Kalyanasundaram, Mohammad Zafar, Bulat A Ziganshin, John A Elefteriades
Journal: Circulation (2022)

Importance: Thoracic aortic dissections (TAD) are a well-known vascular cause of sudden death. Spontaneous coronary artery dissections (SCAD) are emerging as an important cause of early-onset myocardial infarction and sudden death. Genetic variants in multiple connective tissue genes have been recognized to underlie TAD; other genetic variants have similarly been recognized to underlie SCAD. Little data is available regarding any genetic commonality between TAD and SCAD. Objective: To determine any genetic overlap between genes coding for TAD and SCAD. Methods: Extensive review of 17 various retrospective and prospective clinical studies published between 2016 and 2022 exploring genetic studies of TAD and SCAD was performed using PubMed and Orbis. Articles highlighting the significant plausible triggers for TAD or SCAD were analyzed. Separate lists of causative genes were constructed for TAD and SCAD—and then commonalities sought. A Venn diagram was constructed to display the genetic overlap and common physiological pathways involved. Results: We identified a definite, meaningful overlap of fourteen independent genes based on GWAS or other genetic methods. Associated genetic pathways involved various biological processes including: Elastin degradation, smooth muscle cell function and the TGF-pathway. Overlapping genes included the following: COL3A1, TGFB2, SMAD3, MYLK, TGFBR2, TGFBR1, LOX, FBN1, NOTCH1, ELN, COL5A1, COL5A2, COL1A2, MYH11. Corresponding molecular pathways were investigated and correlated for both diseases. Conclusions and relevance: We are not aware of other studies searching for genetic commonalities between TAD and SCAD. We have successfully identified overlapping genes—and their corresponding molecular pathways—for TAD and SCAD. We hope these insights will lead to further clinical and scientific understanding of each disease via study of their fundamental commonalities.
Abstract 11895: Decreased Heart Rate Variability Associated With Hopelessness in Patients With Ischemic Heart Disease
Authors: Madison Goodyke, Tracy Baynard, Ulf G Bronas, Nathan Tintle, Susan L Dunn
Journal: Circulation (2022)

Hopelessness, a negative outlook and sense of helplessness toward the future, is present in 27-52% of patients with ischemic heart disease (IHD) and is associated with increased morbidity and mortality. Physiologic dynamics of hopelessness in patients with IHD are largely unknown. Purpose : To examine how stress adaptation, measured by high frequency (HF) heart rate variability (HRV), following an IHD event may be associated with hopelessness. Subgroup differences focusing on characteristics known to be associated with hopelessness and/or HRV will also be examined (i.e., IHD event, marital status, sex). Hypothesis : Decreased HF HRV will be associated with greater levels of hopelessness. Methods : Participants were enrolled while hospitalized for an IHD event after being identified as appropriate for HRV analysis (n=69). Two weeks after hospital discharge, participants wore a Polar H7 heart rate monitor for 10 minutes while supine for HRV data collection. A demographic questionnaire and State-Trait Hopelessness Scale were then completed. From the 10-minutes of HRV data, a 5-minute HRV segment with the least amount of artifact (&lt;5%) was used for analysis. HRV data was log transformed to account for non-normality. Linear regression was used to assess the relationship between HRV and state hopelessness. Results : There was a moderate negative correlation between HF HRV and state hopelessness (r= -0.35, p=0.004). This remained significant in multivariable regression models when controlling for history of depression and factors known to influence HRV (i.e., time of day, age, and smoking status). No sex differences (Cohen’s d=-0.04, p=0.78) were observed for HF HRV, but persons who underwent bypass surgery had lower HF compared to those that did not (Cohen’s d=0.63, p=0.04). Due to high correlation with HF and root mean square of successive differences between normal heartbeats (rMSSD) and SD1 (r=0.85), patterns of association with hopelessness and those variables were similar throughout. Conclusion : Decreased HF was moderately correlated with increased state hopelessness following an IHD event. Assessing HRV in patients following an IHD event could provide promising evidence of a biomarker to assist in identifying patients at risk for hopelessness.
Abstract 11526: Voltage Gated Sodium Channel β1 Subunit Mimetic Peptide PS2L Increases Regulated Intramembrane Proteolysis of SCN1B/β1
Authors: Zachary Williams, Daniel Hoagland, Jane Jourdan, Robert G Gourdie
Journal: Circulation (2022)

Clinical treatment for cardiac arrhythmias based on targeting ion channels is limited and can have deadly side effects. We previously reported that acute administration of SCN1B mimetic peptide βadp1 resulted in decreased action potential conduction velocity and increased arrhythmias in isolated guinea pig hearts. These changes were associated with disruption of trans-homophilic adhesion of the β1 subunit within gap junction-adjacent perinexal domains in intercalated discs.Following a strategy reported by two other independent groups working on intercellular adhesion molecules containing Ig domains, N-cadherin and desmoglein-2, we dimerized a c-terminal βadp1 sequence resulting in the peptide PS2L.Using Electric Cell-Substrate Impedance Sensing (ECIS) with Chinese Hamster 1610 cells stably expressing β1, we found that PS2L increases β1 mediated adhesion not only acutely, but unexpectedly for over 48 hours post-treatment. Regulated Intramembrane Proteolysis (RIP) of β1 sequentially by BACE-1 and γ-secretase results in a cleaved intracellular fragment that translocates to the nucleus and alters transcription of various genes, including VGSC subunits. Therefore, we hypothesized the long-term gain-of-adhesion-function with PS2L treatment resulted from increased RIP of β1, with downstream VGSC gene expression effects. Inhibition of γ-secretase with DAPT accumulates a C-terminal fragment (CTF) of β1 during RIP, enabling quantification of changes to RIP. Thus, 1610β1 cells were treated with 50μM PS2L, 1μM DAPT, 50μM PS2L+1μM DAPT or 0.1% DMSO control. Cells were fixed for β1 immunofluorescence (IF) or lysate was collected at 6-, 24-, and 48-hours post treatments for Western blotting.IF showed an increase in abundance of β1 48 hours after βadp1 treatment compared to DMSO, especially at cell borders. DAPT treatment significantly increased CTF levels compared to control at all timepoints (p&lt;.0001). However, PS2L+DAPT treatment resulted in greater accumulation of β1 CTF levels over DAPT alone at the 6-hour timepoint but not later. (n=3, p&lt;.05) In sum, our data indicates that PS2L may upregulate RIP of β1 with potential downstream effects on gene transcription of VGSC subunits, suggesting a path to a novel class of antiarrhythmics.
Abstract 12201: Assessing Glycated Hemoglobin (a1c) Thresholds for Development of Cardiovascular Disease by Racial-Ethnic Groups; Insights From a Large Integrated Healthcare System
Authors: Yu Hsin Liu, Maqdooda Merchant, Christopher Low, joseph Vu, Seema Pursnani
Journal: Circulation (2022)

Introduction: Diabetes mellitus (DM) is the strongest risk factor for incident myocardial infarction (MI). Glycated hemoglobin (A1c) is used for diagnosing DM, but racial/ethnic specific A1c diagnostic thresholds do not exist. This study aims to determine whether A1c thresholds for predicting major adverse cardiac events (MACE) differ among racial-ethnic groups in a large, diverse integrated healthcare system. Methods: This is a retrospective cohort study of Kaiser Permanente Northern California members age 30 to 75 without cardiovascular disease for whom A1c during 2014, race/ethnicity data, and 5-year follow-up post A1c were available. Multivariable logistic regression was used to evaluate the odds of MACE (MI, stroke, cardiovascular death) after adjusting for demographic and clinical covariates including age, sex, race, A1c, BMI, smoking, DM meds. Univariate logistic regression with Youden’s index was used to determine A1c thresholds for MACE prediction stratified by race/ ethnicity. Receiver operating characteristic curves were plotted for each equation and a Youden’s index was calculated to determine the race-ethnic specific threshold for prediction of MACE. Results: A1c was associated with an increased odds of MACE (aOR 1.024, 95%CI: 1.022, 1.025). Compared to Whites, South Asian ethnicity was associated with increased odds of MACE (aOR 1.641, 95%CI: 1.456, 1.843). Hispanic (aOR 0.748, 95%CI: 0.702, 0.796) and East Asian ethnicities (aOR 0.804, 95% CI: 0.739, 0.874) were associated with lower odds of MACE. A Youden’s index range of A1c values between 6.0 to 7.3% predicted MACE, with the lowest values seen in Whites (6.0%) and South Asians (6.1%). A1c thresholds for Filipinos, East Asians, Blacks, and Hispanics were 7.3, 6.6, 6.5 and 6.5%, respectively. Conclusions: Our study shows South Asians have a higher odds of MACE compared to Whites. A1c values in a pre-diabetic range predicted MACE in Whites and South Asians, whereas thresholds for MACE prediction were in a diabetic range for other groups. Further studies will help identify whether these trends can be replicated in other geographic areas and influence risk prediction tools.